Investigators in oncology have only recently applied rigorous research methodology to outcomes broader than the traditional efficacy endpoints, tumor response and survival. Dr. Talcott has devoted his career to training, research and teaching patient-oriented "outcomes" research, using quantitative methods and novel endpoints to assess clinical practice. This proposal requests support to allow him to continue and extend his research and teaching activities, to help train a new generation of sophisticated patient-oriented researchers. Prostate cancer and rectal cancer are common visceral malignancies for which pelvic irradiation is appropriate therapy. However, because of unintended but unavoidable damage to nearby radiation-sensitive tissues, it harms normal functioning, particularly urinary, bowel and sexual. In the last 8 years we have studied complications of therapy for prostate cancer in two successive cohorts of over 800 men from before treatment to up to 3 years after. We will use the measurement tools we have developed to compare patient reported toxicity of proton beam therapy compared to conventional photon beam therapy in three randomized Phase III studies, first of rectal cancer and later of early and locally advanced prostate cancer. In addition, we will use the very large, highly detailed databases resulting from the prostate cancer cohort studies, including information on mode of diagnosis collected before treatment, to assess the impact of prostate- specific antigen (PSA) screening on patient outcomes over time. The diagnosis and treatment of prostate cancer has undergone fundamental change since PSA screening became widespread. Use of this blood test, easily added to routine blood test batteries, has led to diagnosis of an additional 100,000 cases of prostate cancer annually, the great majority of which would not result in metastatic disease or death. Further, little unbiased data supports active treatment for early prostate cancer, and all active treatments cause permanent urinary, bowel or sexual symptoms in most men. While several trials are ongoing to determine whether PSA screening prolongs life, growing evidence documents both the important impact of treatments on health-related quality of life and wide variation in patient preferences for treatment and tolerance of treatment-related symptoms. One approach to these issues is to identify differences in outcomes based on the mode of diagnosis (screening vs. investigation of symptoms).